Deviation Plot Research Articles

Will It Be Beneficial To Simulate the Antifreeze Proteins at Ice Freezing Condition or at Lower Temperature?

Antifreeze proteins (AFPs) enable the polar living species to survive subzero temperature conditions through effective lowering of the freezing point of body fluids. At the molecular level, AFPs directly interact with the growing seeds of ice crystals to inhibit their formation. To understand the structural and dynamic aspects of this interaction at the atomistic level, molecular dynamics (MD) simulations were carried out on several type I AFPs at multiple temperatures, including the physiologically relevant temperature of 273 K, a lower temperature of 227 K, and the conventional 300 K. A comparison of the principal component analysis (PCA) and mean squared deviation plots for Winter flounder AFP, HPLC6 (mutant of winter flounder AFP), Sculpin, and peptide 1m AFPs reveals that simulations at 273 and 227 K result in the formation of more conserved metastable states than at 300 K. Other parameters such as root-mean-square deviation (rmsd), solvent accessibility surface area (SASA), H-bonding and residual density function (RDF) also suggest the same. MD simulations with ice crystal, where AFPs are complexed to ice plane with TIP4P/ice water model, help in finding relevance of dynamic behavior, and physiological temperature becomes more pronounced. Additionally, a control study on a nonantifreeze protein (LL37) is included, which aids in exploring significant information. On the basis of this approach, it was found that AFPs at 273 and 227 K display relevant dynamic properties that appear at 300 K for nonantifreeze proteins. The present study hence emphasizes the importance of performing computational simulations for antifreeze proteins at the physiologically relevant temperature (273 K), and even at lower temperatures (like 227 K), rather than at room temperatures (300 K).

Compound Gamma representation for modeling travel time variability in a traffic network

This paper proposes a compound probability distribution approach for capturing both vehicle-to-vehicle and day-to-day variability in modeling travel time reliability in a network. Starting from the observation that standard deviation and mean of distance-normalized travel time in a network are highly positively correlated and their relationship is well characterized by a linear function, this study assumes multiplicative error structures to describe data with such characteristics and derives a compound distribution to model travel delay per unit distance as a surrogate for travel time. The proposed Gamma–Gamma model arises when (within-day) vehicle-to-vehicle travel delay per unit distance is distributed according to a Gamma distribution, with mean that itself fluctuates from day to day following another Gamma distribution. The study calibrates the model parameters and validates the underlying assumptions using both simulated and actual vehicle trajectory data. The Gamma–Gamma distribution shows good fits to travel delay observations when compared to the (simple) Gamma and Lognormal distributions. The main advantage of the Gamma–Gamma model is its ability to recognize different variability dimensions reflected in travel time data and clear physical meanings of its parameters in connection with vehicle-to-vehicle and day-to-day variability. Based on the linearity assumption for the relationship between mean and standard deviation, two shape parameters of the Gamma–Gamma model are linked to the coefficient of variation of travel delay in vehicle-to-vehicle and day-to-day distributions, respectively, and can be directly estimated from the slope of the associated mean-standard deviation plots. An extension of the basic model form was also introduced to address potential deviations from this linearity assumption. The extended Gamma–Gamma model can account for time-of-day variations in mean-standard deviation relationships—such as hysteresis patterns observed in mean and day-to-day variation in travel time—and incorporate such dynamics in travel time distribution modeling. In summary, the model provides a systematic way of quantifying, comparing, and assessing different types of variability, which is important in understanding travel time characteristics and evaluating various transportation measures that affect reliability.

Multi-pass absorption spectroscopy for H2O2 detection using a CW DFB-QCL

Abstract Hydrogen peroxide (H2O2) detection was demonstrated with multi-pass absorption spectroscopy using a commercial 76-m astigmatic multi-pass absorption cell. An ∼7.73-μm continuous wave, distributed feedback quantum cascade laser (CW DFB-QCL) was employed for targeting a strong H2O2 line (1296.2 cm-1) in the fundamental absorption band. Wavelength modulation spectroscopy combined with a second harmonic detection technique was utilized to increase the signal-to-noise ratio. By optimizing the pressure inside the multi-pass cell and the wavelength modulation depth, a minimum detection limit (1σ) of 13.4 ppbv was achieved for H2O2 with a 2-s sampling time. From an Allan-Werle deviation plot, the detection limit could be improved to 1.5 ppbv with an averaging time of 200 s. Interference effects of atmospheric air components are also discussed.

A data-constrained large ensemble analysis of Antarctic evolution since the Eemian

Reconstructing the historical behaviour of the Antarctic Ice Sheet is essential for understanding and predicting climatic interactions, ice sheet sensitivities, and sea level contributions. Furthermore, to interpret such reconstructions with any degree of confidence, meaningful uncertainty estimates are required. Working toward this goal, this article presents results from a large-ensemble data-constrained study of Antarctic evolution over the Last Glacial cycle.Ice sheet chronologies have been generated using a 3-D glacial systems model that includes sheet/stream/shelf flow; a parametrized basal drag coefficient (accounting for sub-grid topographic roughness, sediment likelihood, and systematic model-to-observation thickness misfits); a sub-grid grounding-line flux parametrization; a visco-elastic bedrock response component; parametrized climate forcing; separate shelf and tidewater calving treatments; and a physically-motivated, empirically derived, sub-shelf melt component. There are 31 ensemble parameters to capture uncertainties in the glacial cycle climate, mass-balance processes, and ice dynamics. Once generated, the ensemble of model runs is constrained using a suite of observational data (including constraints on relative sea level, past ice thickness and grounding line retreat data-points, as well as present-day ice volumes and configuration) and an evaluation methodology that produces a misfit-to-observations score for each run. Assuming variants of a Gaussian error model, the scores are used to generate probability distributions for the past evolution of the ice sheet.In our ensemble-based analysis the Last Glacial Maximum (LGM) of Antarctic ice volume occurs at ∼25–24 ka. The LGM ice volume excess relative to present-day is likely between 5.6 and 14.3 m equivalent sea level (mESL), and with less confidence >10 mESL. There is little change in the grounded ice volume from 24 ka until 17–16 ka at which time widespread deglaciation commences. The Ross and Weddell Sea sectors are the largest sources of ice mass loss. The major period of grounding line retreat in the Weddell Sea sector, resulting in the present-day Ronne–Filchner shelf system, occurs after 10 ka; the grounding line in the Ross Sea sector start its major retreat phase after 12 ka. There is no significant contribution (<1.8 mESL) to meltwater pulse 1a.During the Eemian, the modelled Antarctic Ice Sheet has a minimal ice volume at 114 ka contributing ∼2 mESL relative to present-day. The mass loss is principally due to a major retreat of the grounding line in the Siple Coast sector of the Ross Sea.We present standard deviation plots of the ensemble results for present day and at the LGM. These plots highlight geographic areas that would most benefit from additional constraint and therefore offer priorities and guidance for future field campaigns.

Position of the central retinal vessel trunk and location of visual field and parapapillary nerve fibers damage in early to moderate glaucoma

AbstractPurpose To address the question of whether the position of the central retinal vessel trunk (CRVT) exit in the optic disc has a spatial relationship with glaucomatous damageMethods This clinical observational study included patients with early to moderate primary open‐angle glaucoma. The position of the CRVT exit on the lamina cribrosa was evaluated on optic disc photographs. Visual field tests and retinal nerve fibers layer (RNFL) thicknesses, as measured by optical coherence tomography, were evaluated.Results The study included 65 eyes with a CRVT mostly decentered into the nasal region followed by the temporal half of the optic disc. Comparing measurements between the opposite disc quadrants indicated that the RNFL thickness was significantly thinner in the inferotemporal quadrant when the CRVT was located in the superonasal quadrant compared with an exit in the inferonasal (p=0.0183) or temporal (p=0.0039) quadrant. The distance from the CRVT to the nasal disc border was significantly smaller and correlated positively with the occurrence of RNFL abnormality in the temporal region (p=0.0334). Visual field defect incidence was higher in the superonasal quadrant of the pattern deviation plot when the CRVT was located in the superonasal quadrant compared with an exit in the inferonasal quadrant (p&lt;0.0003). Temporal visual field abnormalities occurred more often when the CRVT exit was located in the temporal part of the optic disc than when the CRVT exit was located in the nasal half (p=0.008).Conclusion Local susceptibility for development of glaucomatous damage correlates with the distance to the CRVT, which may act as a stabilizing element against the deformation of the lamina cribrosa.

Letter to the Editor: Quercetin and taxifolin completely break MDM2-p53 association: molecular dynamics simulation study by S. Verma, A. Singh, A. Mishra. Med Chem Res 2013, 22(6) 2778–2787

In their contribution Verma et al. propose a drastic anti-cancer effect of quercetin and taxifolin based on molecular dynamics (MD) simulations of the MDM2-p53 protein complex bound to a ligand. However, we have severe concerns that the observed dissociation of the MDM2-p53 complex is not caused by ligand interaction, but an artifact arising from technical issues of post-processing the simulation data. This becomes evident from the root-mean-square deviation plots versus time of the two ligand-bound protein complex simulations, where huge and immediate jumps indicate analysis problems. In order to corroborate our view, we performed MD simulations of the MDM2-p53 complex without any ligand, which is experimentally known to be stable. We observed similar pseudo-dissociation events in the raw MD data that disappeared after proper post-processing. Thus, we strongly recommend a careful re-analysis of the original raw MD data by the authors. Although we do not exclude a dissociative effect of quercetin and taxifolin onto MDM2-p53, and therefore, potential anti-cancer properties of those compounds, the effect seen in the MD simulations should be much more subtle on that timescale.

Innovative quantitative gait graph consistency assessment with the use of asymmetry vs deviation plots (ADplots)

Innovative quantitative gait graph consistency assessment with the use of asymmetry vs deviation plots (ADplots)

Research on Application of the Television Image Logging Technique in the Englineering Test Borehole

A whole image of a reconnaissance well with acoustic time, acoustic amplitude and video can be obtained by an image logging apparatus. The results (feature dip/strike and azimuth, joint density analysis, synthetic cores, feature stereograms, rose diagrams, deviation plots of borehole) of image logging are displayed in the form of well explained figures, intuitionistic, vivid and easy to be analyzed. Image well logging technique has played an important role in oil and gas exploration, but its application in construction engineering is still in its initial testing phase. The hardware constitution and the basic principle of RG image logging apparatus system are simply introduced, and its application effects in transmission cable tunnel project are also displayed in this paper

Extensive all-atom Monte Carlo sampling and QM/MM corrections in the SAMPL4 hydration free energy challenge

We present our predictions for the SAMPL4 hydration free energy challenge. Extensive all-atom Monte Carlo simulations were employed to sample the compounds in explicit solvent. While the focus of our study was to demonstrate well-converged and reproducible free energies, we attempted to address the deficiencies in the general Amber force field force field with a simple QM/MM correction. We show that by using multiple independent simulations, including different starting configurations, and enhanced sampling with parallel tempering, we can obtain well converged hydration free energies. Additional analysis using dihedral angle distributions, torsion-root mean square deviation plots and thermodynamic cycles support this assertion. We obtain a mean absolute deviation of 1.7kcalmol(-1) and a Kendall's τ of 0.65 compared with experiment.

Disparity between Visual Fields and Optical Coherence Tomography in Hydroxychloroquine Retinopathy

American Academy of Ophthalmology recommendations for screening for hydroxychloroquine (HCQ) retinopathy advise objective measures, such as spectral-domain optical coherence tomography (SD-OCT) and multifocal electroretinography (mfERG) along with visual fields. However, the relative sensitivity and specificity of screening tests have not been fully resolved. We characterize a subset of patients with toxicity who show unusual disparity between fields and SD-OCT and thus have implications for screening practice. Review of charts and clinical data. Patients at Stanford and Kaiser Permanente who had used HCQ with greater than 1000 g cumulative exposure. There were more than 2000 such individuals, among whom 150 had clear evidence of toxicity. Patients were evaluated by visual fields (10-2 white Swedish Interactive Threshold Algorithm pattern deviation plots), SD-OCT, and sometimes mfERG or fundus autofluorescence. Relative findings on visual fields in comparison with SD-OCT. There were 11 patients among those with HCQ toxicity who had parafoveal ring scotomas but a normal-appearing SD-OCT. None had a history of macular disease or evidence for any other cause of bull's eye maculopathy. Conversely, all cases with a clear degree of parafoveal damage on SD-OCT showed at least some focal spots of parafoveal field loss. Approximately 10% of patients with early HCQ toxicity showed prominent ring scotomas on field testing without obvious SD-OCT abnormality. This should encourage the inclusion of visual fields as a key screening tool, even when SD-OCT (a more specific and objective test) also is performed. The combination of visual fields and SD-OCT gives both sensitivity and specificity while avoiding unnecessary stoppage of the drug.

Comparative analysis of binding sites of human meprins with hydroxamic acid derivative by molecular dynamics simulation study

Meprins are complex and highly glycosylated multi-domain enzymes that require post-translational modifications to reach full activity. Meprins are metalloproteases of the astacin family characterized by a conserved zinc-binding motif (HExxHxxGFxHExxRxDR). Human meprin-α and -β protease subunits are 55% identical at the amino acid level, however the substrate and peptide bond specificities vary markedly. Current work focuses on the critical amino acid residues in the non-primed subsites of human meprins-α and -β involved in inhibitor/ligand binding. To compare the molecular events underlying ligand affinity, homology modeling of the protease domain of humep-α and -β based on the astacin crystal structure followed by energy minimization and molecular dynamics simulation of fully solvated proteases with inhibitor Pro-Leu-Gly-hydroxamate in S subsites were performed. The solvent accessible surface area curve shows a decrease in solvent accessibility values at specific residues upon inhibitor binding. The potential energy, total energy, H-bond interactions, root mean square deviation and root mean square fluctuation plot reflect the subtle differences in the S subsite of the enzymes which interact with different residues at P site of the inhibitor.

Assessment of gait kinematic graphs pathology differences, among hemiplegic, diplegic and quadriplegic CP patients using asymmetry vs. deviation plots

Assessment of gait kinematic graphs pathology differences, among hemiplegic, diplegic and quadriplegic CP patients using asymmetry vs. deviation plots

An analytical formulation of thermodynamic properties of dry and metastable steam suitable for computational fluid dynamics modelling of steam turbine flows

Application of computational fluid dynamics to real steam flows including non-equilibrium condensing flows requires an accurate and, at the same time, computationally inexpensive formulation of thermodynamic properties of steam. The present formulation enables fast computation of all thermodynamic properties, using mass density and specific internal energy as independent variables. This choice of independent variables follows the needs of time-marching computational fluid dynamics computations of dry and metastable steam flows in steam turbines. The formulation comprises an ideal-gas part and a residual part. The residual part is expressed in a form analogous to the virial equation of state but the coefficients are functions of internal energy, rather than temperature. Here we present a variant retaining only one coefficient of the density series, corresponding to the second virial coefficient. The uncertainties of properties computed from the present formulation only slightly exceed those of the fundamental formulation IAPWS-95. The formulation is valid from 253.15 K to 1073.15 K. Up to pressures given by the isentrope 7.5 kJ/(kg K), the computed properties are within the experimental uncertainties. Beyond this limit, the accuracy continuously decreases as it can be determined from presented deviation plots.

Stimulus Size for Perimetry in Patients With Glaucoma

Clinical perimetry today uses a stimulus that arose from historic accident. Wall and colleagues1 show that other stimulus choices are at least as valid. Automated static perimetry typically uses the Goldmann size III stimulus, a circular luminance increment whose diameter is 0.43° of visual angle. This choice of stimulus size was not a scientific standard, but was a choice made by the engineers of the first commercial device. Kinetic perimetry had varied both stimulus contrast and stimulus size, but those engineers chose to use a fixed size and a wider range of contrasts. Later companies copied this approach, which became the conventional perimetric stimulus. This approach led to high test–retest variability in glaucomatous defects.2,3 Wall and colleagues1 tested a large number of people with size III, size V (1.72° diameter), a custom “size VI” (3.44° diameter), and with a method that varies stimulus size for a fixed contrast (size threshold perimetry [STP]). They generated their own normative values for each test, and used these to compute total deviation, pattern deviation, and probability plots for the patients. They found the same number of abnormal locations with III, V, and STP, and slightly fewer for size VI. The shapes of defects on probability plots were similar for all tests. Defects were deeper for size III, and variability was higher, consistent with effects of ganglion cell saturation.4 This study is important because it shows that there is nothing special about the use of a single stimulus size, that all of these tests are measuring the same thing. New forms of perimetry are justified that choose stimuli based on desirable properties, such as lower variability and resistance to effects of blur, reduced illumination, and forward light scatter. The perimetry of the 21st century need not be shackled to a historic accident.

SU-D-WAB-05: Image-Based Proton Range Verification Using Intensity-Corrected CBCT

Purpose: Using CBCT to detect variations in proton beam path prior to treatment is an important step in the quality assurance of proton therapy. However, the Hounsfield Units (HUs) from a CBCT differs slightly from a simulation CT, thereby introducing additional uncertainties in the conversion from HUs to proton stopping power. The aim of this work is to demonstrate the feasibility of using deformable image registration to map simulation CT HUs onto a treatment CBCT for range verification during proton therapy. Methods: A simulation CT and two simulated proton CBCT of a head and neck patient were used in this study. We used a diffeomorphic deformable image registration algorithm with symmetric normalization in conjunction with cross correlation similarity metrics (ANTs: Advanced Normalization Tools) to deform the simulation CT onto the CBCTs. Polar plots of proton beam water equivalent thickness (WET) were generated using a ray tracing algorithm at different gantry angles in the unmodified CBCT, corrected CBCT and simulation CT for analysis. Results: With no anatomical variation, corrected CBCT and simulation CT image exhibited excellent agreement in WETs (mean difference of 1.26 mm, interquartile range 0.42∼1.79mm). In the unmodified CBCT image, larger difference in WETs (mean value 3.38 mm, interquartile range 1.90∼5.03mm) attributed to errors in HU to stopping power conversion were observed. With tumor shrinkage the differences in the WET polar plots between planning CT and corrected CBCT correlated with the location of anatomical change in the nasal/oral cavity, indicating potential deviations in proton dose deposition. Conclusion: It is feasible to use deformable image registration to correct CBCT HUs for image based proton range verification. Polar plots of deviations in WET between CBCT and simulation CT is potentially an efficient and practical quality assurance tool in the use of CBCT for proton therapy applications.

Effect of artificial tears on automated visual field testing in patients with glaucoma and dry eye

ObjectiveTo evaluate the effects of artificial tears on automated visual field (VF) testing in patients with glaucoma with dry eye syndrome. DesignProspective study. ParticipantsFifty eyes of 50 patients with medically treated primary open-angle glaucoma (POAG) were recruited for this study. The patients were subdivided into 2 subgroups: those with dry eye syndrome (group I) and those without dry eye syndrome (group II). MethodsTear break-up time, Lissamine green staining, and Schirmer I test with topical anesthesia were performed in the same order in all patients. Ocular Surface Disease Index questionnaire was completed by the patients. All participants underwent automated perimetry using the 24-2 SITA (Swedish interactive threshold algorithm) standard strategy before and after 1-week treatment with a lubricating eye drop 4 times daily. VF results were compared before and after the treatment using Wilcoxon signed rank test, and Mann–Whitney test was performed to compare the results of patients in groups I and II. ResultsOf the 50 patients, 25 (50%) were diagnosed with dry eye syndrome. No significant differences between both groups were found with respect to age (P = 0.779) and glaucoma duration (P = 0.722). In patients with glaucoma with dry eye syndrome, there was a significant improvement in test duration, mean deviation, and the number of depressed points at probability level less than 0.5% and less than 1% in pattern deviation plots after the treatment (P< 0.05). ConclusionsThe use of artificial tears in patients with glaucoma with dry eye syndrome decreased VF testing time and improved test results.

Value of Red Targets and Pattern Deviation Plots in Visual Field Screening for Hydroxychloroquine Retinopathy

To compare the value of red vs white 10-2 visual field testing in patients with different levels of hydroxychloroquine exposure and retinopathy in reference to recent American Academy of Ophthalmology recommendations on screening for hydroxychloroquine retinopathy that advised the use of 10-2 visual field testing with a white test object. We studied retrospectively 13 patients using hydroxychloroquine who had undergone both red (FASTPAC) and white (SITA) 10-2 automated visual field testing in the course of their management. On clinical grounds, they were judged to have no retinopathy, early retinopathy, or moderate or severe hydroxychloroquine retinopathy. White visual field diagrams were difficult to interpret, but pattern deviation plots consistently showed parafoveal sensitivity losses in early retinopathy. Red fields often showed more prominent scotomas in early retinopathy but sometimes showed irregular losses that were hard to evaluate. Either modality showed clear losses in moderate retinopathy. On repeated testing, the pattern deviation plots were somewhat more consistent than red fields in showing parafoveal damage. With white 10-2 visual field hydroxychloroquine screening, the use of pattern deviation plots should be standard practice. Red testing appears to be more sensitive for early retinopathy but may be slightly less specific or consistent. We believe the main application for red testing is in screening for the earliest signs of retinopathy. Either red or white fields should be acceptable for hydroxychloroquine screening, as long as the clinician is sensitive to the characteristic patterns of early parafoveal damage and is prepared to retest fields and add objective tests.

Comparison of SWAP and SAP on the point of glaucoma conversion

BackgroundThe purpose of this study was to compare the two perimetric modalities, SWAP (short wavelength automated perimetry) and SAP (standard automated perimetry), on the point of conversion to glaucoma.MethodsIn this prospective, longitudinal, follow-up study, 282 patients with ocular hypertension were recruited consecutively and tested with both SAP and SWAP annually for 5 years or until the onset of conversion to glaucoma. SAP and SWAP perimetry was performed with the Humphrey Field Analyzer II using the 24-2 full-threshold test. Abnormality for both SAP and SWAP fields was determined on the pattern deviation plot and defined as either a) one point below the 0.5% probability level or b) a cluster of 2 or more points below 1% or c) a cluster of 3 or more points below 2% or d) a cluster of 4 or more points below 5%. Abnormal tests had to be confirmed on a subsequent test within one year to be classified as conversion.ResultsOf the 282 patients initially recruited, 32 were excluded. Of the 250 remaining patients, a total of 38 converted during the follow-up period; 36.8% of conversions were detected earlier with SWAP, 29% simultaneously, and 34.2% were not detected with SWAP during the follow-up period; 2.4% of patients showed SWAP visual field loss that did not result in conversion during the follow-up period.ConclusionThe results in our study are inconclusive. There were patients with earlier, simultaneous, or no SWAP conversion, with SAP conversion as the golden standard criterion. One should consider both SAP and SWAP with confirmation when visual field loss is evident to maximize early detection of glaucoma, because it appears that each method identifies early glaucoma in a subset of patients and these subsets overlap only partially.

The times they are a‐changin’: time to change glaucoma management

The times they are a‐changin’: time to change glaucoma management

Location of visual field defect and optic disc assessment by confocal scanning laser ophthalmoscope in early normal tension glaucoma

AbstractPurpose To compare topographic optic disc measurements in patients with central 10‐degree and outer arcuate visual field (VF) defects in early normal tension glaucoma (NTG)Methods Early NTG patients with a mean deviation of ‐10 dB or better in 24‐2 Humphrey VF analyzer, and glaucomatous optic disc were included in this retrospective study. Patients were divided into central VF defect group (CFD) with VF defect in 10‐degree radius in total deviation plot and peripheral VF defect group (PFD) with outer arcuate VF defect. Global and sectoral optic disc stereometric parameters were obtained with the Heidelberg Retina Tomograph (HRT) III and compared between CFD and PFD group. Mean deviation (MD) of central and nasal peripheral 12 points in mean deviation plot compared between superior and inferior hemifields in both groups.Results Mean deviation and pattern standard deviation values showed no significant difference between 27 patients in the CFD group and 29 patients in the PFD group. The cup area, cup disc area ratio was significantly decreased in CFD group compared to PFD group only in inferotemporal sector, not in other sectoral parameters and global parameters of HRT. The MD of VF in the CFD group was significantly decreased in superior central 6 points (‐9.23±8.12 dB) compared to inferior central 6 points (‐3.36±4.18 dB). The MD of VF in the PFD group showed no significant difference between superior (‐5.24±6.06 dB) and inferior (‐8.10±6.42 dB) nasal peripheral 6 points.Conclusion The change of optic disc in early NTG was more localized in the CFD group than the PFD group and central VF defect was more prominent in the superior hemifield.